The present invention provides methods treating multiple sclerosis (MS) in a patient in need of treatment thereof. The methods comprise co-administering to the patient a fumarate or pharmaceutical acceptable salt thereof, and at least one sulfonylurea or pharmaceutical acceptable salt thereof, where the amount of the fumarate is administered at a dose lower than the therapeutically effective dose if the fumarate is administered alone.

The present invention provides methods treating multiple sclerosis (MS) in a patient in need of treatment thereof. The methods comprise co-administering to the patient a fumarate or pharmaceutical acceptable salt thereof, and at least one sulfonylurea or pharmaceutical acceptable salt thereof, where the amount of the fumarate is administered at a dose lower than the therapeutically effective dose if the fumarate is administered alone.

The present invention provides methods treating multiple sclerosis (MS) in a patient in need of treatment thereof. The methods comprise co-administering to the patient a fumarate or pharmaceutical acceptable salt thereof, and at least one sulfonylurea or pharmaceutical acceptable salt thereof, where the amount of the fumarate is administered at a dose lower than the therapeutically effective dose if the fumarate is administered alone.

An oral dosage form of an antidiabetic pharmaceutical composition comprises a core portion, an outer portion, and a controlled membrane film sandwiched therebetween. The core and outer portions respectively comprise a first antidiabetic agent and a second antidiabetic agent, such as metformin HCl and sitagliptin phosphate, each at a therapeutically effective amount. The controlled membrane film encapsulates the core portion and is provided with at least one passageway for allowing the first antidiabetic agent to release out when the oral dosage form is in an aqueous environment, such as in the gastrointestinal (GI) tract of a subject. The oral dosage form is configured, upon a single-dose oral administration, to provide a maximum plasma concentration of the first antidiabetic agent in the subject from approximately 7.5 to 15 hours after administration. A method for manufacturing the oral dosage form of the antidiabetic pharmaceutical composition is also provided.

An oral dosage form of an antidiabetic pharmaceutical composition comprises a core portion, an outer portion, and a controlled membrane film sandwiched therebetween. The core and outer portions respectively comprise a first antidiabetic agent and a second antidiabetic agent, such as metformin HCl and sitagliptin phosphate, each at a therapeutically effective amount. The controlled membrane film encapsulates the core portion and is provided with at least one passageway for allowing the first antidiabetic agent to release out when the oral dosage form is in an aqueous environment, such as in the gastrointestinal (GI) tract of a subject. The oral dosage form is configured, upon a single-dose oral administration, to provide a maximum plasma concentration of the first antidiabetic agent in the subject from approximately 7.5 to 15 hours after administration. A method for manufacturing the oral dosage form of the antidiabetic pharmaceutical composition is also provided.

Insulin (INS) analogs are disclosed including modifications that increase half-life when compared to native, human INS, that maintain selectivity to the insulin receptor (IR) and that provide in vitro and in vivo stability for improved druggability properties and less immunogenicity. Pharmaceutical compositions also are disclosed that include one or more of the INS analogs described herein in a pharmaceutically acceptable carrier. Methods of making and using the INS analogs also are disclosed, especially for treating metabolic CA conditions, diseases or disorders, especially treating diseases such as diabetes and obesity.

Insulin (INS) analogs are disclosed including modifications that increase half-life when compared to native, human INS, that maintain selectivity to the insulin receptor (IR) and that provide in vitro and in vivo stability for improved druggability properties and less immunogenicity. Pharmaceutical compositions also are disclosed that include one or more of the INS analogs described herein in a pharmaceutically acceptable carrier. Methods of making and using the INS analogs also are disclosed, especially for treating metabolic CA conditions, diseases or disorders, especially treating diseases such as diabetes and obesity.

Disclosed are compounds of Formula 1, ##STR00001##
stereoisomers thereof and pharmaceutically acceptable salts of the compounds and stereoisomers, wherein R.sup.1 and R.sup.2 are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating obesity and related diseases, disorders, and conditions associated with MetAP2.

Disclosed are compounds of Formula 1, ##STR00001##
stereoisomers thereof and pharmaceutically acceptable salts of the compounds and stereoisomers, wherein R.sup.1 and R.sup.2 are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating obesity and related diseases, disorders, and conditions associated with MetAP2.

Methods and compositions are provided that are utilized for treatment and/or prevention of intraventricular hemorrhage or progressive hemorrhagic necrosis (PHN), particularly following spinal cord injury. In particular, the methods and compositions are inhibitors of a particular NC.sub.Ca-ATP channel and include, for example, inhibitors of SUR1 and/or inhibitors of TRPM4. Kits for treatment and/or prevention of intraventricular hemorrhage or progressive hemorrhagic necrosis (PHN), particularly following spinal cord injury, are also provided. The present invention also concerns treatment and/or prevention of intraventricular hemorrhage in infants, including premature infants utilizing one or more inhibitors of the channel is provided to the infant, for example to brain cells of the infant.